给药策略对初始接受低于推荐剂量环磷酰胺治疗的狼疮性肾炎患者临床结局的影响。

Impact of dosing strategy on clinical outcomes of patients with lupus nephritis initially treated with lower-than-recommended-dose cyclophosphamide.

作者信息

Chienwichai Kittiphan, Choomnirat Aniwat, Sangkaew Sorawat, Sunanthamethee Nutthapong, Chang Arunchai

机构信息

Division of Nephrology, Department of Internal Medicine, Hatyai Hospital, Songkhla, Thailand.

Department of Pharmacy, Hatyai Hospital, Songkhla, Thailand.

出版信息

Heliyon. 2024 Sep 2;10(17):e37359. doi: 10.1016/j.heliyon.2024.e37359. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e37359

PMID:39296157

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408774/

Abstract

AIM

Cyclophosphamide is the mainstay treatment for patients with lupus nephritis (LN); it can be prescribed at lower doses than the recommended regimen to avoid side effects. We aimed to investigate the impact of cyclophosphamide dosing strategies on treatment outcomes of patients with LN initially treated with a lower-than-recommended dose.

METHODS

We retrospectively reviewed patients with proliferative LN (class III, IV, or mixed) initially treated with lower-than-recommended-dose cyclophosphamide. Patients who received a titrated dose of cyclophosphamide ≥0.5 g/m were categorized into the titrate group, while those who received doses <0.5 g/m were categorized into the non-titrate group. The primary outcome was primary renal response (PRR) at 52 weeks.

RESULTS

Of the 78 patients included, 47 were assigned to the titrate group and 31 to the non-titrate group. The titrate group had a higher proportion of PRR achievement (23 of 47 patients [48.9 %] vs. 7 of 31 patients [22.6 %] in the non-titrate group). After adjusting for potential confounders, a baseline urinary protein-to-creatinine ratio ≥3 g/g (OR, 0.3; 95 % CI, 0.1-0.9; P = 0.030), and titrating the dose of cyclophosphamide to ≥0.5 g/m (OR, 4.7; 95 % CI, 1.5-15.2; P = 0.010) were independent factors for PRR. Additionally, the titrate group had a lower rate of infection (8 of 47 patients [17.0 %] vs. 12 of 31 patients [38.7 %], respectively; OR, 0.3; 95 % CI, 0.1-0.9; P = 0.036) and death associated with LN (4 of 47 patients [8.5 %] vs. 8 of 31 patients [25.8 %], respectively; OR, 0.3; 95 % CI, 0.1-0.9; P = 0.047) compared with the non-titrate group. LN flare and the need for rescue therapy did not differ between the groups.

CONCLUSION

For patients with LN initially treated with lower-than-recommended-dose cyclophosphamide, titration of the cyclophosphamide dose ≥0.5 g/m was beneficial on renal response, while reducing infection leading to hospitalization and LN-associated death.

摘要

目的

环磷酰胺是狼疮性肾炎（LN）患者的主要治疗药物；可以采用低于推荐方案的剂量给药以避免副作用。我们旨在研究环磷酰胺给药策略对初始接受低于推荐剂量治疗的LN患者治疗结局的影响。

方法

我们回顾性分析了初始接受低于推荐剂量环磷酰胺治疗的增殖性LN（III、IV或混合型）患者。接受环磷酰胺滴定剂量≥0.5 g/m²的患者被归入滴定组，而接受剂量<0.5 g/m²的患者被归入非滴定组。主要结局是52周时的主要肾脏反应（PRR）。

结果

纳入的78例患者中，47例被分配至滴定组，31例被分配至非滴定组。滴定组达到PRR的比例更高（47例患者中的23例[48.9%]，而非滴定组31例患者中的7例[22.6%]）。在对潜在混杂因素进行校正后，基线尿蛋白与肌酐比值≥3 g/g（比值比[OR]，0.3；95%置信区间[CI]，0.1 - 0.9；P = 0.030）以及将环磷酰胺剂量滴定至≥0.5 g/m²（OR，4.7；95% CI，1.5 - 15.2；P = 0.010）是PRR的独立因素。此外，滴定组的感染率较低（分别为47例患者中的8例[17.0%]和31例患者中的12例[38.7%]；OR，0.3；95% CI，0.1 - 0.9；P = 0.036），且与LN相关的死亡率较低（分别为47例患者中的4例[8.5%]和31例患者中的8例[25.8%]；OR，0.3；95% CI，0.1 - 0.9；P = 0.047），与非滴定组相比。两组之间LN复发和抢救治疗的需求无差异。